Split Course Adaptive Radiation Therapy With Pembrolizumab With/Without Chemotherapy for Treating Stage IV Lung Cancer
SiCARIO (Split Course Adaptive Radioimmunotherapy) for the Treatment of Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Using Biologically-Adaptive Radiotherapy - A Phase I/II Study
3 other identifiers
interventional
25
1 country
1
Brief Summary
This phase I/II trial tests the safety and efficacy of split-course adaptive radiation therapy in combination with immunotherapy with or without chemotherapy for the treatment of patients with stage IV lung cancer or lung cancer that that has spread to nearby tissue or lymph nodes (locally advanced). Radiation therapy is a standard cancer treatment that uses high energy rays to kill cancer cells and shrink tumors. Split-course adaptive radiation therapy uses patient disease response to alter the intensity of the radiation therapy. Immunotherapy with monoclonal antibodies such as pembrolizumab, ipilimumab, cemiplimab, atezolizumab or nivolumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs like carboplatin, pemetrexed, and paclitaxel work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving split-course adaptive radiation therapy with standard treatments like immunotherapy and chemotherapy may be more effective at treating stage IV or locally advanced lung cancer than giving them alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2023
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 11, 2022
CompletedFirst Posted
Study publicly available on registry
August 15, 2022
CompletedStudy Start
First participant enrolled
May 9, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2027
ExpectedOctober 17, 2024
October 1, 2024
2.7 years
August 11, 2022
October 16, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events
Safety endpoints will be tabulated using descriptive statistics, and by appropriate subgroups. The incidence of adverse events will be summarized according to organ system in terms of severity by Common Terminology Criteria for Adverse Events and relationship to treatment
Up to 2 years
Best overall response rate
By Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Exact binomial test and 95% confidence interval (CI) will be used.
Within 6 months
Secondary Outcomes (4)
Progression free survival (PFS)
Time from consent to the date of first documentation of objective progressive disease assessed by RECIST 1.1 or death, assessed at 6, 9, and 12 months
Overall survival
Time from consent to the date of death due to any cause, assessed up to 2 years
New metastasis free survival
Time from consent to the date of the first documentation of a new distant metastasis or death, assessed up to 2 years
Quantitative and qualitative markers of planning and treatment resource utilization
Up to 2 years
Study Arms (11)
Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation)
EXPERIMENTALPatients receive carboplatin, pemetrexed, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm II (carboplatin, pemetrexed, cemiplimab, radiation)
EXPERIMENTALPatients receive carboplatin, pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation)
EXPERIMENTALPatients receive carboplatin, paclitaxel and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation)
EXPERIMENTALPatients receive carboplatin, pemetrexed and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation)
EXPERIMENTALPatients receive carboplatin, paclitaxel, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation)
EXPERIMENTALPatients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation)
EXPERIMENTALPatients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm VIII (pembrolizumab, radiation)
EXPERIMENTALPatients receive pembrolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm IX (atezolizumab, radiation)
EXPERIMENTALPatients receive atezolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm X (cemiplimab-rwlc, radiation)
EXPERIMENTALPatients receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Arm XI (nivolumab, ipilumumab, radiation)
EXPERIMENTALPatients receive ipilmumab every 6 weeks and nivolumab every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
Interventions
Correlative studies
Given carboplatin
Undergo PET/CT
Given IV
Given nab-paclitaxel
Given pembrolizumab
Given pemetrexed
Undergo PET/CT
Undergo radiation therapy
Undergo PET scan
Given Ipilimumab
Given Nivolumab
Given Cemiplimab
Eligibility Criteria
You may qualify if:
- Age \>= 18 years at time of informed consent
- Histologically documented or cytologically confirmed diagnosis of stage IVA or IVB (M1b or M1c) or locally advanced (not eligible for standard of care \[SOC\] chemoradiation) non-small cell lung cancer with evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria
- Available tumor material (\< 6 months old) adequate for confirmation of programmed cell death 1 ligand 1 (PD-L1) expression per local standard of care testing
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Adequate organ function to receive therapy as determined by investigators and other treating physicians
- Participants with brain metastases that can be comprehensively managed with surgery and/or stereotactic radiosurgery, prior to initiation of chemo-immunotherapy are allowed. Number of brain metastases allowed is not specified at eligibility is at discretion of investigator
- Contraceptive use should be initiated or continued per guidance in labeling for approved chemotherapies
- Female patients must be non-pregnant and not breastfeeding.
- If woman of childbearing potential (WOCBP), must utilize highly effective contraceptive method (failure rate of \< 1% per year) throughout intervention period and continued per guidance specified in labeling for approved chemotherapies. Must have negative pregnancy test (serum or urine) within 1 week prior to initiation of first cycle of therapy
- Eligible for immunotherapy-based systemic regimens per judgment of patient's study physician
- Able to submit written informed consent
You may not qualify if:
- Mixed small cell histology
- Confirmed candidate (per study physician) for alternative systemic therapy if preferred by treating physician (i.e. mEGFR, ALK, KRAS G12C or ROS1 mutations). Testing not required for enrollment
- Brain metastases that would require administration of whole brain radiotherapy for management on required screening brain MRI within 21 days of day 1 of study treatment
- Symptomatic malignant ascites or malignant pleural effusion (sampling not required). Pleural metastases are allowed if deemed targetable with radiotherapy
- Major surgery (requiring general anesthesia or at discretion of study physician) within 4 weeks prior to study enrollment that would prevent treatment with SiCARIO regimen
- History of organ transplant requiring therapeutic immunosuppression
- Known clinically significant (per study physician) acute or chronic infections including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or active tuberculosis (testing not required). Patients with HBV and HCV must be on stable dose of antiviral therapy on study entry
- Uncontrolled intercurrent illness including, but not limited to, New York Heart Association (NYHA) class III-IV congestive heart failure, uncontrolled hypertension (average systolic blood pressure greater than or equal to 140 or average diastolic blood pressure greater than or equal to 90 despite optimal medical therapy), unstable angina pectoris, cardiac arrythmia, active peptic ulcer disease, bleeding diatheses or psychiatric illness that would limit in the judgment of the study physician
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization within 30 days of day 1 of study treatment
- History of prior independent malignancy within 3 years of enrollment, except for adequately treated basal or squamous cell carcinoma of the skin, adequately treated carcinoma in situ (e.g. cervix or non-invasive bladder cancer)
- Receipt of prior \>1 cycle of immune checkpoint inhibitor for current malignancy (prior cytotoxic chemotherapy is allowed)
- Prior radiotherapy that would preclude delivery of protocol- based radiotherapy to normal organ tolerance per patient's study physician
- Current or prior use of immunosuppressive medications within 28 days of enrollment with exception of intranasal or inhaled corticosteroids or systemic steroids at physiologic doses (equivalent to less than or equal to 10 mg/day of prednisone). Systemic steroids required during therapy for adverse event (AE) management and for residual neurologic complications from management of central nervous system (CNS) metastases are allowed at doses exceeding 10 mg/day of prednisone equivalents
- Active autoimmune disease requiring systemic treatment within past 1 year
- Receipt of live attenuated vaccine within 30 days of enrollment
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Vanderbilt-Ingram Cancer Centerlead
- National Cancer Institute (NCI)collaborator
- Varian Medical Systemscollaborator
Study Sites (1)
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Evan Osmundson, MD, PhD
Vanderbilt University/Ingram Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
August 11, 2022
First Posted
August 15, 2022
Study Start
May 9, 2023
Primary Completion
February 1, 2026
Study Completion (Estimated)
February 1, 2027
Last Updated
October 17, 2024
Record last verified: 2024-10